Microsatellite instability in sporadic carcinomas of the proximal colon: association with diploid DNA content, negative protein expression of p53, and distinct histomorphologic features.
BACKGROUND
Microsatellite instability (MIN) seems to characterize a particular subset of sporadic colorectal adenocarcinomas with the studies indicating a better clinical outcome for patients with MIN-positive tumors than for those with MIN-negative ones. The goal of this study was to further clarify whether a genotype-specific histomorphology of the right-sided colonic carcinomas can be identified.


METHODS
MIN status, DNA content, and p53 protein expression were evaluated in cryoconserved specimens from 20 adenocarcinomas of the proximal colon and correlated to stage, grade, and other histomorphologic features. The study was restricted to tumors of the proximal colon because approximately 90% of all MIN-positive tumors were found in the proximal colon, and differences between right- and left-sided tumors cannot be excluded a priori.


RESULTS
By using four microsatellite markers, instability was detected in 35% of the tumors analyzed. The clinicopathologic features in the MIN-positive tumors were found to differ markedly from the MIN-negative tumors in their poorly differentiated histologic pattern, extracellular mucin production, and favorable lymph node and distant metastatic behavior. A marked association was found between MIN positivity and DNA diploid status, as well as negative p53 immunostaining.


CONCLUSIONS
The MIN-positive colonic carcinomas were characterized by distinct histomorphologic features that are recognizable at routine diagnostic evaluation. Poorly differentiated adenocarcinomas of the proximal colon, with only a few lymph nodes and no distant metastases at presentation, and lack of p53 accumulation are highly suggestive of being MIN positive. These tumors should be discriminated from the other poorly differentiated carcinomas, because they seem to be associated with an improved prognosis compared with the tumors without microsatellite instability.
Forster
S
S
Institute of Human Genetics, University of the Saarland, Homburg, Germany.
Sattler
H P
HP
Hack
M
M
Romanakis
K
K
Rohde
V
V
Seitz
G
G
Wullich
B
B
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002430:Cecal Neoplasms / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015925:Cryopreservation; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D004171:Diploidy; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53